TNKS2: Tankyrase 2 – A Key Regulator of Telomere Maintenance and Wnt Signaling
Comprehensive genomic and functional overview of TNKS2, a PARP family member involved in telomere homeostasis, Wnt/β-catenin signaling, and cancer biology.
Gene Information Card
| Symbol | TNKS2 |
|---|---|
| Full Name | Tankyrase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q23.33 |
| NCBI Gene ID | 80351 ncbi.nlm.nih.gov/gene/80351 |
| Ensembl ID | ENSG00000107854 |
| UniProt ID | Q9H2K2 |
| OMIM ID | 608606 |
| HGNC ID | 11941 |
| Aliases | PARP5B, TANK2, TNKS-2, ARTD6 |
Description
TNKS2 (tankyrase 2) encodes a member of the tankyrase subfamily of poly(ADP-ribose) polymerases (PARPs). The protein contains ankyrin repeats, a sterile alpha motif (SAM), and a PARP catalytic domain. It is involved in telomere length regulation by modifying TRF1, and in Wnt/β-catenin signaling through PARsylation of AXIN. TNKS2 also participates in vesicle trafficking and mitotic spindle assembly.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary breast and ovarian cancer | TNKS2 overexpression may promote Wnt signaling and genomic instability; germline variants are rare but implicated in susceptibility | ClinVar, COSMIC |
| Colorectal cancer | TNKS2 amplification and overexpression enhance β-catenin transcriptional activity; somatic mutations found in tumor samples | COSMIC, NCBI |
| Pancreatic cancer | TNKS2 upregulation correlates with poor prognosis; PARP inhibition of tankyrases is under investigation | NCBI, COSMIC |
| Telomere-related disorders | Dysregulation of TNKS2 affects telomere maintenance; mutations in associated pathways linked to dyskeratosis congenita | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.3 | Medium |
| Lymph node | 7.1 | Medium |
| Brain | 4.2 | Low |
| Liver | 3.8 | Low |
| Heart | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 9.8 | Cervical cancer cell line |
| MCF7 | 7.5 | Breast cancer cell line |
| HCT116 | 11.2 | Colorectal cancer cell line |
| HEK293 | 6.4 | Embryonic kidney cell line |
| K562 | 8.1 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | <0.1% | Alters ankyrin repeat domain; potential impact on protein-protein interactions |
| c.567_568insA (p.Glu190fs) | Frameshift | <0.05% | Loss-of-function; truncation of PARP domain |
| c.2101G>A (p.Gly701Arg) | Missense | 0.2% | Located in PARP domain; may reduce catalytic activity |
| c.3456_3460del (p.Lys1152fs) | Frameshift | <0.1% | Predicted loss of SAM domain; affects oligomerization |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the PARP catalytic domain or SAM domain lead to loss of PARsylation activity and impaired telomere and Wnt signaling regulation.
Gain of Function (GOF)
Missense mutations in the ankyrin repeat region may enhance substrate binding or PARP activity, potentially driving oncogenic Wnt signaling.
Dominant Negative (DN)
Mutations that disrupt the SAM domain can produce truncated proteins that interfere with wild-type tankyrase oligomerization, reducing overall cellular PARsylation capacity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Telomere maintenance (via TRF1 PARsylation)
• Wnt/β-catenin signaling (via AXIN PARsylation and degradation)
• Mitotic spindle assembly
• Vesicle trafficking (via interaction with NUMA and other proteins)
Protein Summary
Tankyrase 2 (TNKS2) is a 1166-amino acid protein with a molecular weight of ~127 kDa. It contains an N-terminal ankyrin repeat domain (mediates substrate binding), a central SAM domain (oligomerization), and a C-terminal PARP catalytic domain (ADP-ribosylation). TNKS2 modifies target proteins such as TRF1, AXIN, and NUMA by adding poly(ADP-ribose) chains, leading to their ubiquitination and degradation. It plays critical roles in telomere length regulation, Wnt signaling, and cell division. Overexpression is observed in multiple cancers, making it a therapeutic target for PARP inhibitors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNKS2 Knockout HEK293 Cell Line | EDJ-KQ9535 | Human | 80351 | Details Get a Quote |
| TNKS2 Knockout A-549 Cell Line | EDJ-KQ36310 | Human | 80351 | Details Get a Quote |
| TNKS2 Knockout HCT 116 Cell Line | EDJ-KQ36311 | Human | 80351 | Details Get a Quote |
| TNKS2 Knockout HeLa Cell Line | EDJ-KQ36312 | Human | 80351 | Details Get a Quote |
